Recent developments in chemistry and biology are indicative of an increased demand for modified biopolymers, such as oligonucleotides, peptides and oligosaccharides. For most applications, oligonucleotides are needed only in small amounts (nano- to milligrams), for use in, e.g., polymerase chain reactions (see, e.g., K. B. Mullis Angew. Chem. 1994, 106, 1271–1276 and K. B. Mullis et al. Methods Enzymol. 1987, 155, 335–3508) and as diagnostic tools (see, e.g., S. Beck et al. Anal. Chem. 1990, 62, 2258–2270; C. Jurinke et al. Anal. Biochem. 1996, 237, 174–181; C. Jurinke et al. Genetic Analysis: Biomolecular Engineering 1996, 13, 67–71; C. Jurinke et al. Anal. Biochem. 1997, 69, 904–910 and C. W. Siegert et al. Anal. Biochem. 1996, 243, 55–65).
There, however, is an increase in uses of biopolymers as therapeutic agents. For example, antisense oligonucleotides (see, e.g., E. Uhlmann et al. Chem. Rev. 1990, 90, 543–584 and F. F. Milligan et al. J. Med. Chem. 1993, 36, 1923–1937) may be used as therapeutic agents. Current methods of biopolymer synthesis, such as solid phase synthesis of oligonucleotides and peptides, result in preparation of small amounts of a desired biopolymer (see, e.g., N. D. Sinha et al. Tetrahedron Lett. 1983, 24, 5843–5846; H. Köster et al. Tetrahedron 1984, 40, 103–112; and N. D. Sinha et al. Nucleic Acids Res. 1984, 12, 4539–4557).
Thus, there is a need for economical large-scale methods of synthesis of modified biopolymers, such as oligonucleotides, peptides and oligosaccharides, that provide the biopolymer with the requisite high purity for therapeutic use. Synthesis in solution offers advantages in large scale production, such as easy upscaling, direct reaction control and purification after each reaction cycle, affording products of high purity. One drawback of solution phase synthesis lies in lower yields, caused by loss of product during purification and incomplete reactions, because reagents cannot be used in large excesses. Known methods of solution phase synthesis of biopolymers also suffer from loss of yield as the length of the biopolymeric chain increased.
A further drawback of solution phase techniques is the lack of solubility of the substrate biopolymer in organic solvents when the number of monomeric units exceeds 3–5. Such lack of solubility also contributes to lower yields seen in solution phase synthesis of biopolymers. Therefore, there is a need for carriers that mediate the solubility of the growing biopolymeric chain.
Therefore, it is an object herein to provide carriers for solution phase synthesis of biopolymers. It is also an object herein to provide methods for biopolymer synthesis using the carriers.